Trial of Adoptive T Cell Therapy With Activated P53 Specific T Cells for Treatment of Advanced Colorectal Cancer
- Conditions
- Colorectal Carcinoma
- Interventions
- Biological: re-activated T cells
- Registration Number
- NCT02577588
- Lead Sponsor
- National Center for Tumor Diseases, Heidelberg
- Brief Summary
The study "Phase I trial of Adoptive T cell Therapy with Activated P53 specific T cells for Treatment of Advanced Colorectal Cancer" is an open label, single arm trial.
- Detailed Description
Most patients with colorectal carcinoma (CRC) accumulate high numbers of endogenous tumor antigen specific cytotoxic and helper memory T cells in their blood. Upon appropriate reactivation, tumor antigen specific T cells can recognize and eliminate autologous tumor cells. This can be achieved ex vivo by their stimulation with antigen pulsed autologous dendritic cells in the absence of regulatory T cells. Upon adoptive transfer, specifically reactivated T cells from cancer patients can efficiently reject autologous human tumors in vivo.
A major target antigen of anti tumor effector T cells in CRC patients is p53, which is overexpressed in many colorectal cancers. Within this clinical trial, high numbers of endogenous tumor specific T cells will be harvested by leukapheresis from the blood of CRC patients harbouring p53-reactive T cells. Isolated T cells will be depleted from regulatory T cells and specifically reactivated for three days ex vivo with three synthetic long peptides containing the most immunogenic regions of p53 using autologous dendritic cells as antigen presenting cells. Activated T cells will be re-infused into the patients.
Ten patients with CRC stage UICC IV under routine first line FOLFOX 6/Bevacizumab therapy are planned to receive a singular treatment with an autologous T cell product at a dose of 5x10\^7 (first three or six patients) or 5x10\^8 (last four or seven patients) cells.
Patient treatment and follow-up will be performed at the National Center for Tumor Diseases (NCT) and at the Department of General, Visceral and Transplantation Surgery, University of Heidelberg. Leukapheresis will take place at the DRK-Blutspendedienst Baden-Württemberg-Hessen in Mannheim and generation of therapeutic cells will be performed at the GMP Unit Cellular Therapy of the DKFZ. Analysis of blood samples with respect to special immune parameters is carried out at the Immune Monitoring Laboratory, Department of Translational Immunology at the NCT, Heidelberg.
The primary objective of this study is to evaluate the safety and tolerability of an adoptive transfer of ex vivo reactivated p53 specific T cells obtained from peripheral blood.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 1
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description re-activated T cells re-activated T cells Ten patients with CRC stage UICC IV under routine first line FOLFOX 6/Bevacizumab therapy are planned to receive a singular treatment with an autologous T cell product at a dose of 5x10\^7 (first three or six patients) or 5x10\^8 (last four or seven patients) cells.
- Primary Outcome Measures
Name Time Method Safety 45 days The primary endpoint is the Dose Limiting Toxicity (DLT), defined as: any adverse event (AE) ≥ Grade 3 according to the Common Terminology Criteria for Adverse Events (CTCAE version 4.03), that is judged by the investigator as definitely, probably or possibly related to the investigational medicinal product (IMP) or to the combination of the IMP and the treatment with FOLFOX 6/Bevacizumab.
- Secondary Outcome Measures
Name Time Method evaluation of p53 specific T cell Responses by analysing data from EliSpot assay day 0, 10, 17, 24, 31 The response of a patient to the p53 peptide mix or to each of the single p53 peptides
Trial Locations
- Locations (1)
National Center for Tumor desease NCT
🇩🇪Heidelberg, BW, Germany